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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorCalvi, Alberto
dc.contributor.authorTur Gomez, Carmen
dc.contributor.authorChard, Declan
dc.contributor.authorStutters, Jonathan
dc.contributor.authorCiccarelli, Olga
dc.contributor.authorCortese, Rosa
dc.date.accessioned2022-09-09T08:40:08Z
dc.date.available2022-09-09T08:40:08Z
dc.date.issued2022
dc.identifier.citationCalvi A, Tur C, Chard D, Stutters J, Ciccarelli O, Cortese R, et al. Slowly expanding lesions relate to persisting black-holes and clinical outcomes in relapse-onset multiple sclerosis. NeuroImage Clin. 2022;35:103048.
dc.identifier.issn2213-1582
dc.identifier.urihttp://hdl.handle.net/11351/8100
dc.descriptionBlack holes; Chronic active lesions; Volumetric MRI
dc.description.abstractBackground Slowly expanding lesions (SELs) are MRI markers of chronic active lesions in multiple sclerosis (MS). T1-hypointense black holes, and reductions in magnetization transfer ratio (MTR) are pathologically correlated with myelin and axonal loss. While all associated with progressive MS, the relationship between these lesion’s metrics and clinical outcomes in relapse-onset MS has not been widely investigated. Objectives To explore the relationship of SELs with T1-hypointense black holes, and longitudinal T1 intensity contrast ratio and MTR, their correlation to brain volume, and their contribution to MS disability in relapse-onset patients. Methods 135 patients with relapsing-remitting MS (RRMS) were studied with clinical assessments and brain MRI (T2/FLAIR and T1-weighted scans at 1.5/3 T) at baseline and two subsequent follow-ups; a subset of 83 patients also had MTR acquisitions. Early-onset patients were defined when the baseline disease duration was ≤ 5 years (n = 85). SELs were identified using deformation field maps from the manually segmented baseline T2 lesions and differentiated from the non-SELs. Persisting black holes (PBHs) were defined as a subset of T2 lesions with a signal below a patient-specific grey matter T1 intensity in a semi-quantitative manner. SELs, PBH counts, and brain volume were computed, and their associations were assessed through Spearman and Pearson correlation. Clusters of patients according to low (up to 2), intermediate (3 to 10), or high (more than 10) SEL counts were determined with a Gaussian generalised mixture model. Mixed-effects and logistic regression models assessed volumes, T1 and MTR within SELs, and their correlation with Expanded Disability Status Scale (EDSS) and confirmed disability progression (CDP). Results Mean age at study onset was 35.5 years (73% female), disease duration 5.5 years and mean time to last follow-up 6.5 years (range 1 to 12.5); median baseline EDSS 1.5 (range 0 to 5.5) and a mean EDSS change of 0.31 units at final follow-up. Among 4007 T2 lesions, 27% were classified as SELs and 10% as PBHs. Most patients (n = 65) belonged to the cluster with an intermediate SEL count (3 to 10 SELs). The percentage of PBHs was higher in SELs than non-SELs (up to 61% vs 44%, p < 0.001) and within-patient SEL volumes positively correlated with PBH volumes (r = 0.53, p < 0.001). SELs showed a decrease in T1 intensity over time (beta = -0.004, 95%CI −0.005 to −0.003, p < 0.001), accompanied by lower cross-sectional baseline and follow-up MTR. In mixed-effects models, EDSS worsening was predicted by the SEL log-volumes increase over time (beta = 0.11, 95%CI 0.03 to 0.20, p = 0.01), which was confirmed in the sub-cohort of patients with early onset MS (beta = 0.14, 95%CI 0.04 to 0.25, p = 0.008). In logistic regressions, a higher risk for CDP was associated with SEL volumes (OR = 5.15, 95%CI 1.60 to 16.60, p = 0.006). Conclusions SELs are associated with accumulation of more destructive pathology as indicated by an association with PBH volume, longitudinal reduction in T1 intensity and MTR. Higher SEL volumes are associated with clinical progression, while lower ones are associated with stability in relapse-onset MS.
dc.language.isoeng
dc.publisherElsevier
dc.relation.ispartofseriesNeuroImage: Clinical;35
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceScientia
dc.subjectEsclerosi múltiple - Imatgeria per ressonància magnètica
dc.subject.meshMultiple Sclerosis, Relapsing-Remitting
dc.subject.mesh/diagnostic imaging
dc.subject.meshMagnetic Resonance Imaging
dc.titleSlowly expanding lesions relate to persisting black-holes and clinical outcomes in relapse-onset multiple sclerosis
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1016/j.nicl.2022.103048
dc.subject.decsesclerosis múltiple recurrente-remitente
dc.subject.decs/diagnóstico por imagen
dc.subject.decsimagen por resonancia magnética
dc.relation.publishversionhttps://doi.org/10.1016/j.nicl.2022.103048
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Calvi A, Chard D, Stutters J, Ciccarelli O] Queen Square MS Centre, Department of Neuroinflammation, Institute of Neurology, Faculty of Brain Sciences, University College London (UCL), United Kingdom. [Tur C] Queen Square MS Centre, Department of Neuroinflammation, Institute of Neurology, Faculty of Brain Sciences, University College London (UCL), United Kingdom. Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. [Cortese R] Dep. of Medicine, Surgery and Neuroscience, University of Siena, Italy
dc.identifier.pmid35598462
dc.identifier.wos000828057500004
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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